The main goal of this proposal is to bring a variety of approaches based on genetically modified mice to bear on the study of how genes control synapse formation, synaptic fine tuning, learning, memory, emotional state, and long-term synaptic plasticity. In so doing, we will be testing, in a number of different and synergistic ways, one central idea; that several, seemingly distinct and apparently unrelated biological processes - development, the fine tuning of a sensory representation in the brain, memory storage and stress related depressive states - reflect, to a large extent, a common set of molecular, genetic, and cellular mechanisms that are expressed in different contexts and in distinct neural circuits. Underlying and unifying these diverse processes is the central importance of long-term synaptic plasticity.